The major objectives of our research are (1) to measure in infant and adult mice the smallest amount of glutamate (GLU) that accumulates in the arcuate nucleus of the hypothalamus (ARH) to produce neuronal necrosis, (2) to determine if there is a time in gestation when the brains of fetal mice are unaffected by Glu, (3) to ascertain why GABA, glutamine and alanine are not toxic in the CNS, (4) to determine if other toxic amino acids accumulate in the ARH like Glu, and (5) to compare the effects on consummatory behavior of radio frequency lesions and those produced by excitatory amino acids. Results will contribute to our understanding of placental barriers to amino acids and will give a better understanding of CNS regional blood-brain-barriers to specific amino acids and how these change with age. Comparisons of rates of CNS uptake and maximal levels reached and time course of return to control levels will be made between Glu and Asp, both of which are neurotoxins. Data will be obtained to determine if nontoxic amino acids are accumulated in the ARH like Glu which is neurotoxic. Results obtained from studies in which experimentally produced lesions are made will enable us to evaluate the importance of an intact neuronal and/or neuroglial system in maintaining function "regulated by" lesioned areas. Results from these experiments go beyond those in which tissue slices or whole brain are used because quantitative histochemical measurements will be made in histologically homogeneous brain areas. Long term goals of this research are to measure the metabolism of neurotoxic amino acids in the ARH and liver, how patterns of metabolism vary with age, and to study behavioral abnormalities which may be produced by neurotoxic amino acids and localizing subcortical neuronal destruction.